title: Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials.
abstract: BACKGROUND
  A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors.
  
  
  METHODS
  MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor.
  
  
  RESULTS
  Eighty-five trials (21,708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac-cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI + ARB versus monotherapy.
  
  
  CONCLUSIONS
  ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardiovascular risk factor is warranted.
authors.affiliation: Department of Pharmacology and Clinical Epidemiology, Mario Negri Sud Consortium, S. Maria Imbaro (Ch), Italy.
authors.forename: Ausilia
authors.initials: A
authors.lastname: Maione
authors.forename: Sankar D
authors.initials: SD
authors.lastname: Navaneethan
authors.forename: Giusi
authors.initials: G
authors.lastname: Graziano
authors.forename: Ruth
authors.initials: R
authors.lastname: Mitchell
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Antonio
authors.initials: A
authors.lastname: Nicolucci
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Antonio
authors.initials: A
authors.lastname: Sasso
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.forename: Valeria Maria
authors.initials: VM
authors.lastname: Manfreda
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gentile
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D000419:Albuminuria / Q000139:chemically induced* / Q000401:mortality; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000401:mortality; D048909:Diabetes Complications / Q000139:chemically induced; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors